Polymer-micelle complex as an aid to electrospinning

ABSTRACT

A polymer-micelle complex suitable for use as an aid to preparing fibers, particularly nanofibers, by electrospinning. The polymer-micelle complex may be designed to impart viscosity, surface tension and conductivity properties optimal for electrospinning. By incorporating the complex as a secondary ingredient, one may electrospin sparingly soluble or low molecular weight polymers. Moreover, the polymer-micelle complex can be used as a generic carrier for preparing fibers incorporating other desired materials, such as rigid or globular (hard-to-spin) polymers, enzymes, cells, viral particles and nanoparticles.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit under 35 U.S.C. 119(e) ofU.S. Provisional Patent Application Ser. No. 60/881,712, filed Jan. 22,2007, the disclosure of which is incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The invention described herein may be manufactured and used by or forthe government of the United States of America for governmental purposeswithout the payment of any royalties thereon or therefor.

BACKGROUND OF THE INVENTION

The present invention relates generally to the electrospinning offibers, especially nanofibers, and relates more particularly to anelectrospinning aid that promotes the electrospinning of one or moredesired materials into fibers, particularly nanofibers.

Nanofibers are fibers with a diameter in the nanoscale range, typicallyfrom about 10 nanometers to about several hundred nanometers. Becausenanofibers possess many desirable physical and chemical properties, suchas a high surface-to-volume ratio and an ability to be modified and/orfunctionalized, nanofibers are desirable in many different types ofapplications including, but not limited to, textiles, membrane systems,catalysis, immobilized enzymes, chemical and biological defense,fiber-reinforced composite materials, HEPA (High Efficiency ParticulateArrestance) filters, tissue engineering, wound healing, sensors andphotonics. Examples of such applications are disclosed in the followingpatents and publications, all of which are incorporated herein byreference: U.S. Pat. No. 6,106,913, inventors Scardino et al., issuedAug. 22, 2000; U.S. Pat. No. 6,110,590, inventors Zarkoob et al., issuedAug. 29, 2000; U.S. Pat. No. 6,800,155 B2, inventors Senecal et al.,issued Oct. 5, 2004; U.S. Patent Application Publication No. US2001/0045547 A1, inventors Senecal et al., published Nov. 29, 2001; U.S.Patent Application Publication No. US 2002/0081732 A1, inventors Bowlinet al., published Jun. 27, 2002; U.S. Patent Application Publication No.US 2002/0096246 A1, inventors Sennet et al., published Jul. 25, 2002;U.S. Patent Application Publication No. US 2002/0124953 A1, inventorsSennett et al., published Sep. 12, 2002; U.S. Patent ApplicationPublication No. US 2002/0173213 A1, inventors Chu et al., published Nov.21, 2002; U.S. Patent Application Publication No. US 2003/0065355 A1,inventor Weber, published Apr. 3, 2003; U.S. Patent ApplicationPublication No. US 2003/0100944 A1, inventors Laskin et al., publishedMay 29, 2003; and Li et al., “Electrospun nanofibrous structure: A novelscaffold for tissue engineering,” J. Biomed. Mater. Res., 60:613-21(2002); Huang et al., “A review on polymer nanofibers by electrospinningand their applications in nanocomposites,” Composites Science andTechnology, 63:2223-53 (2003); Katti et al., “BioresorbableNanofiber-Based Systems for Wound Healing and Drug Delivery:Optimization of Fabrication Parameters,” J. Biomed. Mater. Res.,70B:286-96 (2004).

Nanofibers may be produced by a number of different techniques, such asinterfacial polymerization, melt-spinning, and electrospinning. Thebasic process of electrospinning was invented about 70 years ago byFormhals and is disclosed in U.S. Pat. No. 1,975,504, which isincorporated herein by reference. Additional patents relating toelectrospinning include U.S. Pat. No. 4,043,331, inventors Martin etal., which issued Aug. 23, 1977; U.S. Pat. No. 4,143,196, inventors Simmet al., which issued Mar. 6, 1979; and U.S. Pat. No. 4,323,525, inventorBornat, which issued Apr. 6, 1982, all of which are incorporated hereinby reference. Until about fifteen years ago, electrospinning hadreceived relatively little attention as a process for producing verythin fibers. However, since that time, interest in electrospinning,particularly the electrospinning of nanofibers, has increasedconsiderably. See, for example, Jin et al., “Electrospinning Bombyx moriSilk with Poly(ethylene oxide),” Biomacromolecules, 3:1233-39 (2002); Liet al., “Electrospinning of Nanofibers: Reinventing the Wheel?,” Adv.Mater., 16(14):1151-70 (2004); Arayanarakul et al., “Effects ofPoly(ethylene glycol), Inorganic Salt, Sodium Dodecyl Sulfate, andSolvent System on Electrospinning of Poly(ethylene oxide),” Macromol.Mater. Eng., 291:581-91 (2006), all of which are incorporated herein byreference.

Referring now to FIG. 1 of the present application, the technique ofelectrospinning is schematically shown. A quantity of a polymer solution11 (such a polymer solution often referred to in the art as a “spindope”) is loaded into the barrel 13 of a syringe. A needle 15 isattached to the distal end of barrel 13, and a plunger 17, which may bedriven by a pump (not shown), is inserted into the proximal end ofbarrel 13. As plunger 17 displaces solution 11 from barrel 13, a dropletof solution 11 becomes suspended from the tip of needle 15, where thedroplet is held in place by surface tension forces. An electrode 19 froma high voltage power supply 21 is in contact with needle 15 and appliesan electric potential thereto, which electric potential induces freecharges in polymer solution 11. These free charges, in turn, introduce atensile force in polymer solution 11. When the tensile force overcomesthe surface tension associated with the pendant drop of polymer solution11 at the tip of needle 15, a jet of polymer solution 11 is ejected fromthe tip of needle 15. Fluid mechanic analysis of thisphenomenon-suggests that the jet of polymer solution 11 experiencesvarious instabilities depending upon the operating conditions and theproperties of fluids. In most cases, the jet experiences a whippinginstability giving rise to the bending and stretching of the jet. As thejet travels the short distance (typically about 20 cm) between the tipof needle 15 and a grounded collector 23, the contour length of the jetdramatically increases by orders of magnitude, and the jet thins to thenanometer scale. The solvent in the jet evaporates as the jet travelsfrom the tip of needle 15 to collector 23. This evaporation of thesolvent leaves dry nanofibers on the surface of collector 23. Typically,the dry nanofibers are deposited on the surface of collector 23 in theform of a nonwoven or random mat of nanofibers; however, it is alsopossible, for example, using a collector in the form of a rotatingcylinder, to collect the nanofibers as a spool of nanofibers.

Uniform nanofibers are not typically produced from all polymersolutions. Instead, the morphology and other properties of anelectrospun nanofiber may be influenced by one or more of the following:(i) properties of the polymer solution, such as viscosity, dielectricconstant, surface tension, density and solvent vapor pressure, (ii)operational variables, such as the solution flow rate, the appliedelectric field and the electric current, and (iii) equipment variables,such as the needle size and the distance between the needle and thecollector. The stability of the jet emitted from the needle depends onthe viscous and viscoelastic properties of the polymer solution. Polymersolutions of low viscosity tend to produce unstable jets that break intodroplets and form beaded structures, as opposed to fibers. On the otherhand, polymer solutions having reduced surface tension tend to formfibers, as opposed to beads. Also, fluid mechanic analysis has shown adirect dependence of the fiber diameter on the surface tension of thepolymer solution. Moreover, electrical forces are responsible for theinitiation of the jet and the stretching during whipping instability.Therefore, high solution conductivity and large solvent dielectricconstant tend to favor thinner fibers.

Approximately 50 different polymers, some synthetic—some biological,have been used to form electrospun nanofibers. Various differentsolvents, some aqueous—others non-aqueous, have been used with thesepolymers to produce polymer solutions suitable for electrospinning. Inthe past, the primary consideration that has been used in selecting asolvent has been whether the polymer can dissolve in the solvent in alarge enough concentration to make the solution sufficiently viscous.(As noted above, if the polymer solution is insufficiently viscous, thejet tends to break into droplets and form beaded structures, instead offibers.) As a result, many polymers that have low aqueous solubility orthat have low molecular weight do not typically generate the necessaryviscosity in an aqueous solution and, instead, have been dissolved innon-aqueous solvents, if at all. Unfortunately, however, the use of manynon-aqueous solvents is undesirable from an environmental point of view,especially if one considers the large-scale production of nanofibers.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an electrospinningaid that may be used to permit the electrospinning of one or moredesired materials into fibers, particularly nanofibers.

The present invention is based on the discovery that, by including asuitable polymer-micelle complex in a spin dope, one can electrospinfibers to include materials that may not otherwise be capable of beingelectrospun into fibers, either in a particular solvent or in anysolvent. Consequently, for example, sparingly soluble polymers, lowmolecular weight polymers, rigid or globular polymers, as well as othermaterials, such as nanoparticles, enzymes, cells, and viral particles,are now capable of being incorporated into electrospun fibers. Onebenefit of the invention is that, for example, if one wishes toelectrospin fibers from an aqueous spin dope, as opposed to anon-aqueous spin dope, one can now do so.

Therefore, according to one aspect of the invention, there is provided amethod of forming a fiber, the fiber including a desired material, themethod comprising the steps of (a) providing a spin dope, the spin dopeincluding (i) a solvent, (ii) a polymer-micelle complex, thepolymer-micelle complex being present in the solvent in a quantitysufficient to enable the spin dope to be electrospun into a fiber, and(iii) a desired material present in the solvent; and (b) electrospinningthe spin dope into a fiber comprising the desired material.

The present invention is also directed at fibers made by theaforementioned method and at the spin dope used in the aforementionedmethod.

Additional objects, as well as features and advantages, of the presentinvention will be set forth in part in the description which follows,and in part will be obvious from the description or may be learned bypractice of the invention. The embodiments will be described insufficient detail to enable those skilled in the art to practice theinvention, and it is to be understood that other embodiments may beutilized and that structural changes may be made without departing fromthe scope of the invention. The following detailed description is,therefore, not to be taken in a limiting sense, and the scope of thepresent invention is best defined by the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are hereby incorporated into andconstitute a part of this specification, illustrate various embodimentsof the invention and, together with the description, serve to explainthe principles of the invention. In the drawings wherein like referencenumerals represent like parts:

FIG. 1 is a simplified schematic diagram illustrating the technique ofelectrospinning;

FIG. 2( a) is a schematic diagram, illustrating polymer-micellecomplexation;

FIG. 2( b) is a graph, depicting the changes in relative viscosity for aspin dope as a function of surfactant concentration for polymers ofdifferent molecular weights; and

FIGS. 3( a) through 3(e) are SEM images of electrospun nanofibersproduced according to various experiments described in Example 2.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention is directed at the use of a polymer-micellecomplex as an aid to electrospinning fibers. In particular, the presentinvention is based on the discovery that, by including a suitablepolymer-micelle complex in a spin dope, one can electrospin fibers toinclude one or more materials that may not otherwise be capable of beingelectrospun into fibers, either in a particular solvent or in anysolvent. Consequently, for example, materials that may not otherwise beelectrospinnable into fibers from an aqueous spin dope may now beelectrospun into fibers by including in the aqueous spin dope apolymer-micelle complex that is, itself, capable of being electrospuninto fibers.

In view of the above, a spin dope according to the present inventionincludes the following components: (i) a solvent; (ii) anelectrospinning aid in the form of a polymer-micelle complex dispersedin the solvent in a quantity sufficient to render the spin dopeelectrospinnable into fibers; and (iii) one or more materials ofinterest present in the solvent for incorporation into the electrospunfibers.

The solvent may be a pure solvent or may be a mixture of solvents. Forthe reasons discussed above, it may be desirable for the solvent to bewater. However, the present invention is not limited to an aqueoussolvent and may alternatively consist of or may additionally include oneor more polar or non-polar non-aqueous solvents, such as, but notlimited to, sulfuric acid, nitric acid, carbon tetrachloride, benzene,ortho-xylene, para-xylene, mixed xylene isomers, formic acid, dimethylformamide, N,N-dimethyl formamide, N,N-dimethyl acetamide, chloroform,tetrahydrofuran, methylene chloride, ethanol, methanol, isopropanol,hydrochloric acid, camphorsulfonic acid, trifluoroacetic acid,dichloromethane, toluene, acetone, methylethylketone, carbon disulfide,hexafluoro-2-propanol, and hexafluoroisopropanol.

The surface tension of water is typically about 72 mN/m, which isgenerally not particularly favorable for generating thin, uniformfibers. On the other hand, water has a dielectric constant of about78.4, which is favorable for charging the jet and electrostaticstretching to make thin fibers. The electrical conductivity of waterdepends on the extent to which ionic species are present therein. If,for example, salt is added to the water, the electrical conductivitywill increase. (10 mM salt will result in a conductivity of about 60mS/m.) For the non-aqueous solvents listed above, the surface tension istypically in the range of about 20 to 40 mN/m, the dielectric constantis typically in the range of about 5 to 40, and the electricconductivity is typically quite small, typically below about 4 mS/m (inmost cases, below 1 mS/m).

As noted above, the electrospinning aid of the present invention is inthe form of a polymer-micelle complex. Consequently, one needs to selecta polymer and a surfactant that, when added to the particular solvent inquestion, will form a polymer-micelle complex and will render the spindope suitable for electrospinning (for example, by making the spin dopeappropriately viscous). The polymer may be a polymer that, even in theabsence of the surfactant, is electrospinnable in the particular solventselected, but this need not be the case. In fact, one of the benefits ofemploying a polymer-micelle complex in accordance with the presentinvention is that the range of solvents in which the polymer may beelectrospun may be expanded. For example, by selecting an appropriatesurfactant, a polymer that would not otherwise be electrospinnable froman aqueous solvent may be rendered electrospinnable. In fact, by virtueof the formation of a polymer-micelle complex, polymers that hithertohave not been capable of being electrospun may now be electrospinnable.

A schematic representation of the polymer-micelle complex involving anonionic polymer, such as polyethylene oxide, and an ionic surfactant,such as sodium dodecyl sulfate, in water is presented in FIG. 2( a). Ascan be seen, the segments of the polymer molecule wrap around thesurfactant micelles with the polymer segments partially penetrating thepolar head group region of the micelles and reducing the micellecore-water contact. A single polymer molecule can interact with one ormore micelles depending upon the molecular weight of the polymer. Thesize of the polymer-bound micelle depends on the nature ofpolymer-micelle interactions. The formation of polymer-micelle complexgives rise to gross conformational changes in the polymer molecule andresulting changes in solution viscosity. The ionic micelles make thenonionic polymer behave like a polyelectrolyte because of inter-micellerepulsions and contribute to significant expansion of the polymer coilupon complex formation. The solution viscosity thus dramaticallyincreases. As the surfactant concentration continues to increase, theionic strength of the solution also increases, which reduces theinter-micelle repulsions and causes a reduction in the magnitude ofpolymer expansion. As a result, the solution viscosity first increases,exhibits a maximum and then decreases with increasing concentration ofthe surfactant.

The polymer used in the polymer-micelle complex may consist of a singlepolymer species or may include a plurality of polymer species. Each suchpolymer may be a synthetic polymer or may be a naturally-occurringpolymer, such as a polypeptide, DNA, or other biopolymer. Examples ofpolymers that may be used to form the polymer-micelle complex include,but are not limited to, the following: polyethylene oxide (PEO);polyvinyl pyrrolidone (PVP); polyvinyl alcohol (PVOH); polyamides (PA);polyurethanes (PU); polybenzimidazole (PBI); polycarboate (PC);polyacrylonitrile (PAN); polylactic acid (PLA);polyethylene-co-vinyl-acetate (PEVA); polymethacrylate(PMMA)/tetrahydroperfluorooctylacrylate (TAN); collagen-PEO; polyaniline(PANI)-PEO; PANI/polystyrene (PS); polyvinylcarbazole; polyethyleneterephthalate (PET); polyacrylic acid-polypyrene methanol (PAA-PM);polystyrene (PS); polymethacrylate (PMMA); polyvinyl phenol; polyvinylchloride (PVC); cellulose acetate (CA); polyacrylamide, collagen, silk;polycaprolactone; poly(2-hydroxyethyl methacrylate); poly(vinylidenefluoride); polyether imide; poly(lactide-co-glycolide); hydroxylpropylcellulose (HPC); polypropylene oxide (PPO); ethyl hydroxylethylcellulose (EHEC); and polymetha-phenylene isophthalamide.

The surfactant used in the polymer-micelle complex may consist of asingle surfactant species or may include a plurality of surfactantspecies. The surfactant is present in the spin dope in a quantitysufficient not only to form micelles but also to cause polymer-micellecomplexation to an extent needed to increase the viscosity of the spindope, as compared to a corresponding spin dope lacking the surfactant.Depending upon the type of solvent and the type of polymer, examples ofsuitable surfactants may include ionic surfactants, such as, but notlimited to, fluorocarbon surfactants, alkyl aryl sulfonates (e.g.,alkylbenzenesulfonates), polyalkoxy carboxylates, N-acylsarcosinates,acylated protein hydrolysates, short-chain alkylarenesulfonates,lignosulfonates, napththalenesulfonates, α-olefinsulfonates, petroleumsulfonates, dialkyl sulfosuccinates, amidosulfonates, 2-sulfoethylesters of fatty acids, fatty acid ester sulfonates, alcohol sulfates,ethoxylated alcohol sulfates, sulfated alkylphenol ethoxylates, sulfatedacids, amides, and esters, sulfated natural oils and fats, phosphateesters, and the like, and combinations thereof, and nonionicsurfactants, such as, but not limited to, alcohol ethoxylates,alkylphenol ethoxylates, glycerol esters, polyoxyethylene esters,ethoxylated anhydrosorbitol esters, natural ethoxylated fats, oils, andwaxes, glycol esters of fatty acids, alkyl polyglycosides,diethanolamine condensates, monoalkanolamine condensates,polyoxyethylene fatty acid amides, fatty acid glucamides, polyalkyleneoxide block copolymers, poly(oxyethylene-co-oxypropylene) andcombinations thereof. For purposes of the present invention, a micellemay include a mixture of surfactant species, such as a mixture of ionicsurfactant molecules and nonionic surfactant molecules.

The choice of the surfactant mainly controls the surface tension of thespin dope since the surface tension reduction with the surfactant ismuch larger than the reduction achieved with the polymer alone. Forexample, compared to a surface tension of about 72 mN/m for water, asolution containing polymer-SDS micelles may have a surface tension ofabout 35 mN/m. Typically, surface tension values in the range of 30 to40 mN/m are attainable with hydrocarbon type surfactants. If fluorinatedsurfactants are used, then surface tensions in the range of 17 to 24mN/m can be achieved. The conductivity of the aqueous solution dependson the concentration of the surfactant. For aqueous solutions of SDS,the electrical conductivity has been measured to be about 33 mS/m at 5mM SDS, 60 mS/m at 10 mM SDS, and 75 mS/m at 16 mM SDS. Similar valuesare achieved for various ionic surfactants, both of the hydrocarbon typeand the fluorocarbon type. Thus, the solution containing polymer-micellecomplex can be designed to have viscosity, surface tension andconductivity properties covering a wide range, suitable forelectrospinning, by the choice of the polymer-micelle complex system.

The various conditions under which polymer-micelle complexes form havebeen extensively studied, as exemplified by the following documents, allof which are incorporated herein by reference: U.S. Pat. No. 6,524,485B1, inventors Dubin et al., which issued Feb. 25, 2003; Nagarajan etal., “Viscometric Investigation of Complexes Between Polyethyleneoxideand Surfactant Micelles,” Polymer Preprints, 23(1):41 et seq. (1982);Nagarajan, “Thermodynamics of Nonionic Polymer-Micelle Association,”Colloids and Surfaces, 13:1-17 (1985); Goddard, “Polymer-SurfactantInteraction Part I. Uncharged Water-Soluble Polymers and ChargedSurfactants,” Colloids and Surfaces, 19:255-300 (1986); Nagarajan,“Association of nonionic polymers with micelles, bilayers, andmicroemulsions,” J. Chem. Phys., 90(3): 1980-94 (1989); Nagarajan,“Polymer-Surfactant Interactions,” New Horizons: Detergents for the NewMillenium Conference Invited Papers,” published by American Oil ChemistsSociety and Consumer Specialty Products Association, Fort Myers, Fla.(2001); Barany, “Interaction between Water Soluble Polymers andSurfactants,” Macromol. Symp., 166:71-92 (2001); Gasbarrone et al.,“Interactions of short-chain surfactants with a nonionic polymer,”Colloid Polym Sci, 279:1192-9 (2001); Wettig et al., “Studies of theInteraction of Cationic Gemini Surfactants with Polymers and TriblockCopolymers in Aqueous Solution,” Journal of Colloid and InterfaceScience, 244:377-385 (2001); Zanette et al., “The Role of theCarboxylate Head Group in the Interaction of Sodium Dodecanoate withPoly(ethylene oxide) Investigated by Electrical Conductivity, Viscosity,and Aggregation Number Measurements,” Journal of Colloid and InterfaceScience, 246:387-92 (2002); Mya et al., “Effect of Ionic Strength on theStructure of Polymer-Surfactant Complexes,” J. Phys. Chem. B. 107:5460-6(2003); Bernazzani et al., “On the Interaction of Sodium Dodecyl Sulfatewith Oligomers of Poly(Ethylene Glycol) in Aqueous Solution,” J. Phys.Chem. B, 108:8960-9 (2004); and Mészáros et al., “Effect of PolymerMolecular Weight on the Polymer/Surfactant Interaction,” J. Phys. Chem.B, 109:13538-44 (2005). Consequently, one of ordinary skill in the artwill be able to determine readily which combinations of polymers andsurfactants are appropriate for use with a given solvent in order torender a spin dope electrospinnable.

The one or more materials of interest added to the spin dope mayinclude, but are not limited to, sparingly soluble or low molecularweight polymers, rigid or globular (hard-to-spin) polymers, enzymes,cells, drugs, viral particles and nanoparticles. In general, anymaterial that can be added to the spin dope and remain dispersed thereinduring electrospinning may be used. In fact, if desired, the materialmay be contained within the micelle, itself, which may be desirable ifthe material is a drug, an enzyme or other material whose activity onewishes to control. Hard-to-spin polymers include, but are not limitedto, repeat sequence protein polymers (RSPPs), for example, thosedescribed in WO 2005/094868, published Oct. 13, 2005, which is herebyincorporated by reference in its entirety. The repeating units also maybe derived from naturally occurring proteins and synthetic repeatingamino acid sequences units may be utilized as well, such as silk-elastinpolymers and copolymers (SELP). SELP47K finds use as a repeat sequenceprotein polymer of the present invention, and is a homoblock proteinpolymer that consists exclusively of silk-like crystalline blocks andelastin-like flexible blocks. SELP47K is 70% proline, valine, andalanine. Other silk-elastin polymer examples and variants include, butare not limited to, SELP 47E, SELP 47R, SELP 47K, SELP 47E, SELP 27K,SELP37K, SELP 67K, and SELP 58. The repeat sequence protein polymers,including SELPs, may be obtained or produced as described in WO2005/094868.

It should be understood that, although the present invention isparticularly advantageous when used to electrospin materials that, inthe absence of the polymer-micelle complex, are not electrospinnableinto fibers in the particular solvent being used, the one or morematerials of interest are not so limited and may include materials that,in the absence of the polymer-micelle complex, may be electrospun intofibers in the particular solvent being used.

The following examples are provided for illustrative purposes only andare in no way intended to limit the scope of the present invention:

Example 1

The relative viscosities of a number of polyethylene oxide-surfactantsolutions (relative viscosity being defined as the ratio between theviscosity of the polymer and surfactant solution and the viscosity ofthe polymer solution, both at the same polymer concentration) weredetermined experimentally. The results are plotted in FIG. 2( b) as afunction of the surfactant concentration for the anionic surfactantsodium dodecyl sulfate interacting with different molecular weights andconcentrations of polyethylene oxide. (The circles represent a highmolecular polymer, the squares represent a low molecular weight polymer,and the diamonds represents an intermediate molecular weight polymer.)

As can be seen, the viscosity data show that the polymer molecularweight, polymer concentration, and surfactant concentration arevariables that can be manipulated to obtain any desired viscosity value.In general, the lower the polymer molecular weight, the higher thepolymer and surfactant concentrations are needed to attain the sameviscosity level.

Example 2

To illustrate how a polymer-micelle complex may be used as an aid toelectrospinning, Applicants investigated the electrospinning of a gelforming, silk-elastin biopolymer, SELP (Genencor International, Inc.,Rochester, N.Y.). SELP is a genetically engineered repeat block ofcopolymer of protein sequences representative of silk and elastin. Ithas the structure H₂N—(S₃E₃E_(K)E₄S₃)₁₋₁₃—COOH, where S stands for thesilk-like peptide block GAGAGS (SEQ ID NO: 1), E stands for theelastin-like peptide block GVGVP (SEQ ID NO: 2) and E_(K) stands for themodified elastin-like peptide block, GKGVP (SEQ ID NO: 3). The molecularweight of the polymer is about 70,000 Dalton. The protein polymers arewater-soluble and they form irreversible gels due to physicalinteractions if the polymer concentration is large enough—even atambient temperatures. The rate of gelation is dependent on the polymercomposition, concentration, temperature and other solution conditions.The gelation is indeed exploited for developing the polymer gels forcontrolled drug delivery applications. However, the onset of gelformation is sufficient to cause problems with electrospinning. Gelationis avoided or at least the rate of gelation is retarded only when theaqueous phase concentration is decreased. However, this would cause thesolution viscosity to also decrease below a level suitable forelectrospinning.

SELP biopolymer is soluble in formic acid without the formation of anygels. Applicants have electrospun SELP from a 15 weight percent solutionin formic acid using a set-up shown in FIG. 1. The applied voltage was20 kV and the polymer solution flow rate was maintained at 120 μl/h. Thedistance between the nozzle end and the collector surface wasapproximately 15 cm, and a grounded aluminum foil was used as thecollector. Nanofibers of 200 to 300 nm diameter were produced as shownby the SEM image in FIG. 3( a). No bead formation was observed. One canobserve a few spots where fiber-fiber contact had occurred between notfully dry fibers. Applicants have electrospun the same system but at alower polymer concentration of about 8 weight percent such that theviscosity of the solution will be lower. The resulting electrospunnanofibers are shown in FIG. 3( b). One can see significant presence ofbeads forming in the system.

An aqueous solution of SELP was prepared at about 6.7 weight percent forwhich no gelation was observed over the duration of our experiments.However, the solution viscosity was quite small and this could not beprocessed into fibers by electrospinning. Applicants added 2.1 weightpercent polyethylene oxide (MW=900,000) and 1 weight percent sodiumdodecyl sulfate (approximately 35 mM) to this solution. Thepolymer-micelle complex formation was spontaneous and the solutionbecame significantly viscous. The polymer PEO contributed to increasingthe solution viscosity so that fibers could be generated in preferenceto beads. The addition of the surfactant SDS increased the solutionviscosity further by the formation of extended PEO-SDS micellecomplexes, decreased the surface tension of the solution, increased thesolution conductivity and also increased the clouding/gelationtemperatures, thus retarding any possible gelation. Nanofibers in thesize range 200 to 300 nm in diameter were formed as shown by the SEMimage in FIG. 3( c).

To make the above-described fibers resistant to contact with water, thesecondary structure of silk-like blocks was modified to induce formationof a larger fraction of hydrogen-bonded beta sheets or beta strands.This was done by treatment of the fibers with methanol. As shown in FIG.3( d), the nanofiber morphology of the treated fibers was notsignificantly modified. The fibers were swollen somewhat compared to theuntreated fibers. An alternate approach involved thermal annealing. Inthis approach, the fibers were thermally annealed at 140 C for 30minutes, which resulted in some fiber swelling but no gross changes infiber morphology as can be seen from the SEM image in FIG. 3( e).

In these preliminary experiments, no attempt has been made to optimizethe polymer-micelle complex. It is clear from FIG. 2( b) that, bychoosing a higher molecular weight PEO, one can formulate anelectrospinnable aqueous solution at much lower concentrations of bothPEO and SDS.

It may be desirable to use a very high molecular weight polymer inapplications where one wishes to electrospin polymers of low molecularweights, polymers with low aqueous solubilities, or polymers that haverigid or globular chain elements. This will keep the polymer-micellecomplex as a secondary ingredient with relatively small mass fractions.In the above example, the polymer-micelle complex accounts for a massfraction of about 0.32 in the total solids; however, by using a PEO ofabout MW=5×10⁶, the polymer-micelle mass fraction could have beenreduced to less than 0.10. For applications where one wishes toelectrospin proteins and nanoparticles, it may desirable to use polymersof a lower molecular weight. This will allow an adequate amount of solidmaterial to be available to act as the template to incorporate thecompact proteins and nanoparticles.

The embodiments of the present invention recited herein are intended tobe merely exemplary and those skilled in the art will be able to makenumerous variations and modifications to it without departing from thespirit of the present invention. All such variations and modificationsare intended to be within the scope of the present invention as definedby the claims appended hereto.

1. A method of forming a fiber, the fiber including a desired material,the method comprising the steps of: (a) providing a spin dope, the spindope including (i) a solvent, (ii) a polymer-micelle complex, thepolymer-micelle complex being present in the solvent in a quantitysufficient to enable the spin dope to be electrospun into a fiber, and(iii) a desired material present in the solvent; and (b) electrospinningthe spin dope into a fiber comprising the desired material.
 2. Themethod as claimed in claim 1 wherein the solvent consists of water. 3.The method as claimed in claim 1 wherein the solvent comprises water. 4.The method as claimed in claim 3 wherein the solvent further comprises anon-aqueous solvent.
 5. The method as claimed in claim 1 wherein thesolvent consists of at least one non-aqueous solvent.
 6. The method asclaimed in claim 5 wherein the at least one non-aqueous solvent isselected from the group consisting of sulfuric acid, nitric acid, carbontetrachloride, benzene, ortho-xylene, para-xylene, mixed xylene isomers,formic acid, dimethyl formamide, N,N-dimethyl formamide, N,N-dimethylacetamide, chloroform, tetrahydrofuran, methylene chloride, ethanol,methanol, isopropanol, hydrochloric acid, camphorsulfonic acid,trifluoroacetic acid, dichloromethane, toluene, acetone,methylethylketone, carbon disulfide, hexafluoro-2-propanol, andhexafluoroisopropanol.
 7. The method as claimed in claim 1 wherein thepolymer-micelle complex comprises a single polymer species.
 8. Themethod as claimed in claim 1 wherein the polymer-micelle complexcomprises a plurality of polymer species.
 9. The method as claimed inclaim 1 wherein the polymer-micelle complex comprises a syntheticpolymer.
 10. The method as claimed in claim 1 wherein thepolymer-micelle complex comprises a naturally-occurring polymer.
 11. Themethod as claimed in claim 1 wherein the polymer-micelle complexcomprises a polymer that, in the absence of the polymer-micelle complex,cannot be electrospun in the solvent into fibers of desired size ormorphology.
 12. The method as claimed in claim 1 wherein the polymer isselected from the group consisting of polyethylene oxide (PEO);polyvinyl pyrrolidone (PVP); polyvinyl alcohol (PVOH); polyamides (PA);polyurethanes (PU); polybenzimidazole (PBI); polycarboate (PC);polyacrylonitrile (PAN); polylactic acid (PLA);polyethylene-co-vinyl-acetate (PEVA); polymethacrylate(PMMA)/tetrahydroperfluorooctylacrylate (TAN); collagen-PEO; polyaniline(PANI)-PEO; PANI/polystyrene (PS); polyvinylcarbazole; polyethyleneterephthalate (PET); polyacrylic acid-polypyrene methanol (PAA-PM);polystyrene (PS); polymethacrylate (PMMA); polyvinyl phenol; polyvinylchloride (PVC); cellulose acetate (CA); polyacrylamide, collagen, silk;polycaprolactone; poly(2-hydroxyethyl methacrylate); poly(vinylidenefluoride); polyether imide; poly(lactide-co-glycolide); hydroxylpropylcellulose (HPC); polypropylene oxide (PPO); ethyl hydroxylethylcellulose (EHEC); and polymetha-phenylene isophthalamide.
 13. The methodas claimed in claim 1 wherein the polymer-micelle complex comprises asingle surfactant species.
 14. The method as claimed in claim 1 whereinthe polymer-micelle complex comprises a plurality of surfactant species.15. The method as claimed in claim 14 wherein the polymer-micellecomplex comprises a micelle that includes a mixture of surfactantspecies.
 16. The method as claimed in claim 1 wherein the one or moredesired materials are selected from the group consisting of sparinglysoluble or low molecular weight polymers, rigid or globular polymers,enzymes, cells, drugs, viral particles and nanoparticles.
 17. The methodas claimed in claim 1 wherein the one or more desired materials, in theabsence of the polymer-micelle complex, cannot be electrospun in thesolvent into fibers of desired size or morphology.
 18. The method asclaimed in claim 1 wherein the one or more desired materials arecontained within the micelle of the polymer-micelle complex.
 19. A fiberproduced according to the method of claim
 1. 20. The fiber as claimed inclaim 19 wherein the fiber is a nanofiber.
 21. A spin dope suitable forbeing electrospun into fibers that include one or more desiredmaterials, the spin dope comprising: (a) a solvent, (b) apolymer-micelle complex, the polymer-micelle complex being present inthe solvent in a quantity sufficient to enable the spin dope to beelectrospun into a fiber, and (c) a desired material present in thesolvent.
 22. The spin dope as claimed in claim 21 wherein the solventconsists of water.
 23. The spin dope as claimed in claim 21 wherein thesolvent comprises water.
 24. The spin dope as claimed in claim 23wherein the solvent further comprises a non-aqueous solvent.
 25. Thespin dope as claimed in claim 21 wherein the solvent consists of atleast one non-aqueous solvent.
 26. The spin dope as claimed in claim 21wherein the polymer-micelle complex comprises a single polymer species.27. The spin dope as claimed in claim 21 wherein the polymer-micellecomplex comprises a plurality of polymer species.
 28. The spin dope asclaimed in claim 21 wherein the polymer-micelle complex comprises asynthetic polymer.
 29. The spin dope as claimed in claim 21 wherein thepolymer-micelle complex comprises a naturally-occurring polymer.
 30. Thespin dope as claimed in claim 21 wherein the polymer-micelle complexcomprises a polymer that, in the absence of the polymer-micelle complex,cannot be electrospun in the solvent into fibers of desired size ormorphology.
 31. The spin dope as claimed in claim 21 wherein thepolymer-micelle complex comprises a single surfactant species.
 32. Thespin dope as claimed in claim 21 wherein the polymer-micelle complexcomprises a plurality of surfactant species.
 33. The spin dope asclaimed in claim 32 wherein the polymer-micelle complex comprises amicelle that includes a mixture of surfactant species.
 34. The spin dopeas claimed in claim 21 wherein the one or more desired materials areselected from the group consisting of sparingly soluble or low molecularweight polymers, rigid or globular polymers, enzymes, cells, drugs,viral particles and nanoparticles.
 35. The spin dope as claimed in claim21 wherein the one or more desired materials, in the absence of thepolymer-micelle complex, cannot be electrospun in the solvent intofibers of desired size or morphology.
 36. The spin dope as claimed inclaim 21 wherein the one or more desired materials are contained withinthe micelle of the polymer-micelle complex.